Improved methods for converting cannabidiol into delta8-tetrahydrocannabinol

ABSTRACT

Disclosed herein a method for converting (cannabidiol) CBD into a composition comprising Δ8-tetrahydrocannabinol (Δ8-THC) and Δ9-tetrahydrocannabinol (Δ9-THC), in which the composition has a Δ8-THC:Δ9-THC ratio that is greater than 1.0:1.0. The method comprises contacting the CBD with a Lewis-acidic heterogeneous reagent under protic, aprotic, or neat reaction conditions comprising: (i) a reaction temperature that is greater than a threshold reaction temperature for the Lewis-acidic heterogeneous reagent and the solvent system; and (ii) a reaction time that is greater than a threshold reaction time for the Lewis-acidic heterogeneous reagent, the solvent system, and the reaction temperature.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to and benefit of U.S. ProvisionalPatent Application Ser. No. 62/860,097 filed on Jun. 11, 2019, which ishereby incorporated by reference.

TECHNICAL FIELD

The present disclosure generally relates to methods for isomerizingcannabinoids. In particular, the present disclosure relates to methodsfor converting cannabidiol into Δ⁸-tetrahydrocannabinol or mixtures ofΔ⁸-tetrahydrocannabinol and Δ⁹-tetrahydrocannabinol.

BACKGROUND

Since the discovery of specific receptors for cannabinoids in mammalianbrain and peripheral tissues, cannabinoids have attracted renewedinterest for medicinal and recreational applications. In particular,Δ⁹-tetrahydrocannabinol (Δ⁹-THC) has been the focus of numerous studies.For example, Dronabinol—a synthetic form of Δ⁹-THC—is currently beinginvestigated for a wide variety of therapies relating to glaucoma,arthritis, chronic pain, cancer, multiple sclerosis, and other diseases.

Δ⁸-tetrahydrocannabinol (Δ⁸-THC) is a regioisomer of Δ⁹-THC and,relative to Δ⁹-THC, Δ⁸-THC has received relatively little attention.Notably, the cannabinoid-receptor-binding affinity for Δ⁸-THC is similarto that of Δ⁹-THC, but Δ⁸-THC is reported to be approximately 50% lesspotent in terms of psychoactivity. Hence, methods for forming Δ⁸-THCselectively are attractive, but there is a paucity of information inthis respect. There is also a paucity of information on methods thatprovide mixtures of Δ⁸-THC and Δ⁹-THC in which Δ⁸-THC is the majorproduct. Instead, the vast majority of methods for preparing THC areaimed at forming Δ⁹-THC selectively, and little is known about thetherapeutic and/or recreational utility of mixtures of Δ⁸-THC and Δ⁹-THCin which Δ⁸-THC is more than a minor component.

Δ⁸-THC and Δ⁹-THC can both be prepared from cannabidiol (CBD). However,known methods for converting CBD to Δ⁸-THC and/or Δ⁹-THC typicallyemploy chemicals that are dangerous, and/or toxic. Moreover, suchmethods typically rely on protocols that are generally consideredhazardous and/or not suitable for industrial scale reactions (e.g.reagent-addition, quenching, and/or work-up steps that are highlyexothermic). Several known methods for converting CBD to Δ⁸-THC and/orΔ⁹-THC also require special care to eliminate oxygen and moisture fromthe reaction vessel for optimal reactivity and safety. Accordingly,improved methods of converting CBD into Δ⁹-THC and/or Δ⁸-THC aredesirable.

SUMMARY

The present disclosure provides improved methods of convertingcannabidiol (CBD) into primarily Δ⁸-tetrahydrocannabinol (Δ⁸-THC) ormixtures of Δ⁸-THC and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) havingΔ⁸-THC:Δ⁹-THC ratios of greater than 1.0:1.0. The methods of the presentdisclosure are suitable for use at industrial scale in that they do notrequire: (i) complicated and/or dangerous reagent-addition, quenching,and/or work-up steps; and (ii) dangerous and/or toxic solvents and/orreagents. Importantly, the methods of the present disclosure provideaccess to compositions with wide-ranging Δ⁸-THC:Δ⁹-THC ratios asevidenced by the wide-ranging Δ⁸-THC:Δ⁹-THC ratios disclosed herein.Because the Δ⁸-THC:Δ⁹-THC ratios disclosed herein can be correlated toparticular reaction conditions and reagents, the methods of the presentdisclosure can be tuned towards particular Δ⁸-THC/Δ⁹-THC selectivityoutcomes.

The present disclosure asserts that the ability to form primarily Δ⁸-THCand/or compositions of various Δ⁸-THC:Δ⁹-THC ratios which are greaterthan 1.0:1.0 as demonstrated herein is associated with the utilizationof Lewis-acidic heterogeneous reagents. Results disclosed hereinindicate that slight changes to reaction conditions involvingLewis-acidic heterogeneous reagents can be leveraged to provideparticular Δ⁸-THC/Δ⁹-THC selectivities. The utilization of Lewis-acidicheterogeneous reagents for the present transformations also appears tobe compatible with the use of class III solvents (or neat reactionconditions) which may obviate the need for the dangerous and/orhazardous solvents that are typical of the prior art. The utilization ofLewis-acidic heterogeneous reagents may also allow product mixtures tobe isolated by simple solid/liquid separations (e.g. filtration and/ordecantation). As such, the utilization of Lewis-acidic heterogeneousreagents appears to underlie one more of the advantages of the presentdisclosure.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, in whichthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.In such embodiments, the method may comprise contacting the CBD with aLewis-acidic heterogeneous reagent under reaction conditions comprising:(i) an aprotic-solvent system; (ii) a reaction temperature that isgreater than a threshold reaction temperature for the Lewis-acidicheterogeneous reagent and the aprotic-solvent system; and (iii) areaction time that is greater than a threshold reaction time for theLewis-acidic heterogeneous reagent, the aprotic-solvent system, and thereaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC. In such embodiments, the methodmay comprise contacting the CBD with a Lewis-acidic heterogeneousreagent under reaction conditions comprising: (i) an aprotic-solventsystem; (ii) a reaction temperature that is greater than a thresholdreaction temperature for the Lewis-acidic heterogeneous reagent and theaprotic-solvent system; and (iii) a reaction time that is greater than athreshold reaction time for the Lewis-acidic heterogeneous reagent, theaprotic-solvent system, and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, in whichthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.In such embodiments, the method may comprise contacting the CBD with aLewis-acidic heterogeneous reagent under neat reaction conditionscomprising: (i) a reaction temperature that is greater than a thresholdreaction temperature for the Lewis-acidic heterogeneous reagent; and(ii) a reaction time that is greater than a threshold reaction time forthe Lewis-acidic heterogeneous reagent and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC. In such embodiments, the methodmay comprise contacting the CBD with a Lewis-acidic heterogeneousreagent under neat reaction conditions comprising: (i) a reactiontemperature that is greater than a threshold reaction temperature forthe Lewis-acidic heterogeneous reagent; and (ii) a reaction time that isgreater than a threshold reaction time for the Lewis-acidicheterogeneous reagent and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, in whichthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.In such embodiments, the method may comprise contacting the CBD with aLewis-acidic heterogeneous reagent under reaction conditions comprising:(i) a protic-solvent system; (ii) a reaction temperature that is greaterthan a threshold reaction temperature for the Lewis-acidic heterogeneousreagent and the protic-solvent system; and (iii) a reaction time that isgreater than a threshold reaction time for the Lewis-acidicheterogeneous reagent, the protic-solvent system, and the reactiontemperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC. In such embodiments, the methodmay comprise contacting the CBD with a Lewis-acidic heterogeneousreagent under reaction conditions comprising: (i) a protic-solventsystem; (ii) a reaction temperature that is greater than a thresholdreaction temperature for the Lewis-acidic heterogeneous reagent and theprotic-solvent system; and (iii) a reaction time that is greater than athreshold reaction time for the Lewis-acidic heterogeneous reagent, theprotic-solvent system, and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC. In such embodiments, the methodmay comprise contacting the CBD with an ion-exchange resin underreaction conditions comprising: (i) a class III solvent; (ii) a reactiontemperature that is greater than about 60° C.; and (iii) a reaction timethat is greater than about 60 minutes.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, in whichthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.In such embodiments, the method may comprise contacting the CBD with analuminosilicate-based reagent under reaction conditions comprising: (i)a class III solvent; (ii) a reaction temperature that is greater thanabout 70° C.; and (iii) a reaction time that is greater than about 60minutes.

Other aspects and features of the present disclosure will becomeapparent to those ordinarily skilled in the art upon review of thefollowing description of specific embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a high-performance liquid chromatogram for EXAMPLE 1.

FIG. 2 shows a high-performance liquid chromatogram for EXAMPLE 2.

FIG. 3 shows a high-performance liquid chromatogram for EXAMPLE 3.

FIG. 4 shows a high-performance liquid chromatogram for EXAMPLE 4.

FIG. 5 shows a high-performance liquid chromatogram for EXAMPLE 5.

FIG. 6 shows a high-performance liquid chromatogram for EXAMPLE 6.

FIG. 7 shows a high-performance liquid chromatogram for EXAMPLE 7.

FIG. 8 shows a high-performance liquid chromatogram for EXAMPLE 8.

FIG. 9 shows a high-performance liquid chromatogram for EXAMPLE 9.

FIG. 10 shows a high-performance liquid chromatogram for EXAMPLE 10.

FIG. 11 shows a high-performance liquid chromatogram for EXAMPLE 11.

FIG. 12 shows a high-performance liquid chromatogram for EXAMPLE 12.

FIG. 13 shows a high-performance liquid chromatogram for EXAMPLE 13.

DETAILED DESCRIPTION

As noted above, the present disclosure provides improved methods forconverting a first cannabinoid into primarily a second cannabinoid ormixtures of a second cannabinoid and a third cannabinoid in which thesecond cannabinoid:third cannabinoid ratio is greater than 1.0:1.0. Themethods of the present disclosure are suitable for use at industrialscale in that they do not require: (i) complicated and/or dangerousreagent-addition, quenching, and/or work-up steps; and (ii) dangerousand/or toxic solvents and/or reagents. Importantly, the methods of thepresent disclosure provide access to compositions having wide-rangingsecond cannabinoid:third cannabinoid ratios as evidenced by thewide-ranging second cannabinoid/third cannabinoid selectivity disclosedherein. For example, a first set of reaction conditions disclosed hereinprovides a second cannabinoid:third cannabinoid ratio of about 1.5:1.0,and a second set of reaction conditions disclosed herein provides asecond cannabinoid:third cannabinoid ratio of about 19.2:1.0. Becausethe reagents and reaction conditions disclosed herein can be correlatedto particular second cannabinoid:third cannabinoid ratios, the methodsof the present disclosure may be tuned towards particular secondcannabinoid/third cannabinoid selectivity outcomes. While there may belittle information available in the current research literature onpharmacokinetic interactions between mixtures of isomeric cannabinoidshaving defined ratios, the present disclosure asserts that access to anarray of compositions of wide-ranging isomeric ratios is desirable inboth medicinal and recreational contexts. Moreover, the presentdisclosure asserts that access to an array of compositions of varyingisomeric ratios is desirable to synthetic chemists.

Without being bound to any particular theory, the present disclosureasserts that the ability to convert a first cannabinoid into primarily asecond cannabinoid that is an isomer of the first cannabinoid or into acomposition comprising isomeric cannabinoids in various ratios asdemonstrated herein is associated with the utilization of Lewis-acidicheterogeneous reagents. Results disclosed herein indicate that slightchanges to reaction conditions involving Lewis-acidic heterogeneousreagents can be leveraged to provide particular isomeric selectivities.The utilization of Lewis-acidic heterogeneous reagents also appears tobe compatible with the use of class III solvents (or neat reactionconditions) which may obviate the need for the dangerous and/orhazardous solvents that are typical of the prior art. The utilization ofLewis-acidic heterogeneous reagents may also allow product mixtures tobe isolated by simple solid/liquid separations (e.g. filtration and/ordecantation). As such, the utilization of Lewis-acidic heterogeneousreagents appears to underlie one more of the advantages of the presentdisclosure.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, whereinthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0,the method comprising contacting the CBD with a Lewis-acidicheterogeneous reagent under reaction conditions comprising: (i) anaprotic-solvent system; (ii) a reaction temperature that is greater thana threshold reaction temperature for the Lewis-acidic heterogeneousreagent and the aprotic-solvent system; and (iii) a reaction time thatis greater than a threshold reaction time for the Lewis-acidicheterogeneous reagent, the aprotic-solvent system, and the reactiontemperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC, the method comprising contactingthe CBD with a Lewis-acidic heterogeneous reagent under reactionconditions comprising: (i) an aprotic-solvent system; (ii) a reactiontemperature that is greater than a threshold reaction temperature forthe Lewis-acidic heterogeneous reagent and the aprotic-solvent system;and (iii) a reaction time that is greater than a threshold reaction timefor the Lewis-acidic heterogeneous reagent, the aprotic-solvent system,and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, whereinthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0,the method comprising contacting the CBD with a Lewis-acidicheterogeneous reagent under neat reaction conditions comprising: (i) areaction temperature that is greater than a threshold reactiontemperature for the Lewis-acidic heterogeneous reagent; and (ii) areaction time that is greater than a threshold reaction time for theLewis-acidic heterogeneous reagent and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC, the method comprising contactingthe CBD with a Lewis-acidic heterogeneous reagent under neat reactionconditions comprising: (i) a reaction temperature that is greater than athreshold reaction temperature for the Lewis-acidic heterogeneousreagent; and (ii) a reaction time that is greater than a thresholdreaction time for the Lewis-acidic heterogeneous reagent and thereaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, whereinthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0,the method comprising contacting the CBD with a Lewis-acidicheterogeneous reagent under reaction conditions comprising: (i) aprotic-solvent system; (ii) a reaction temperature that is greater thana threshold reaction temperature for the Lewis-acidic heterogeneousreagent and the protic-solvent system; and (iii) a reaction time that isgreater than a threshold reaction time for the Lewis-acidicheterogeneous reagent, the protic-solvent system, and the reactiontemperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into primarily Δ⁸-THC, the method comprising contactingthe CBD with a Lewis-acidic heterogeneous reagent under reactionconditions comprising: (i) a protic-solvent system; (ii) a reactiontemperature that is greater than a threshold reaction temperature forthe Lewis-acidic heterogeneous reagent and the protic-solvent system;and (iii) a reaction time that is greater than a threshold reaction timefor the Lewis-acidic heterogeneous reagent, the protic-solvent system,and the reaction temperature.

In select embodiments, the present disclosure relates to a method forconverting CBD into Δ⁸-THC, the method comprising contacting the CBDwith an ion-exchange resin under reaction conditions comprising: (i) aclass III solvent; (ii) a reaction temperature that is greater thanabout 60° C.; and (iii) a reaction time that is greater than about 60minutes.

In select embodiments, the present disclosure relates to a method forconverting CBD into a composition comprising Δ⁸-THC and Δ⁹-THC, whereinthe composition has a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0,the method comprising contacting the CBD with an aluminosilicate-basedreagent under reaction conditions comprising: (i) a class III solvent;(ii) a reaction temperature that is greater than about 70° C.; and (iii)a reaction time that is greater than about 60 minutes.

In the context of the present disclosure, the term “contacting” and itsderivatives is intended to refer to bringing the CBD and theLewis-acidic heterogeneous reagent as disclosed herein into proximitysuch that a chemical reaction can occur. In some embodiments of thepresent disclosure, the contacting may be by adding the Lewis-acidicheterogeneous reagent to the CBD. In some embodiments, the contactingmay be by combining, mixing, or both.

In the context of the present disclosure, the term “CBD” refers tocannabidiol or, more generally, cannabidiol-type cannabinoids.Accordingly the term “CBD” includes: (i) acid forms, such as “A-type”,“B-type”, or “AB-type” acid forms; (ii) salts of such acid forms, suchas Na⁺ or Ca²⁺ salts of such acid forms; (iii) ester forms, such asformed by hydroxyl-group esterification to form traditional esters,sulphonate esters, and/or phosphate esters; (iv) various double-bondisomers, such as Δ¹-CBD and Δ⁶-CBD as well as cis/trans isomers thereof;and/or (v) various stereoisomers. In select embodiments of the presentdisclosure, the CBD is a component of a distillate, an isolate, aconcentrate, an extract, or a combination thereof. In select embodimentsof the present disclosure, CBD may have the following structuralformula:

In the context of the present disclosure, the term “Δ⁹-THC” refers toΔ⁹-tetrahydrocannabinol or, more generally, Δ⁹-tetrahydrocannabinol-typecannabinoids. Accordingly the term “Δ⁹-THC” includes: (i) acid forms,such as “A-type”, “B-type”, or “AB-type” acid forms; (ii) salts of suchacid forms, such as Na⁺ or Ca²⁺ salts of such acid forms; (iii) esterforms, such as those formed by hydroxyl-group esterification to formtraditional esters, sulphonate esters, and/or phosphate esters; and/or(iv) various stereoisomers. Δ⁹-THC may have the following structuralformula:

In the context of the present disclosure, the term “Δ⁸-THC” refers toΔ⁸-tetrahydrocannabinol or, more generally, Δ⁸-tetrahydrocannabinol-typecannabinoids. Accordingly the term “Δ⁸-THC” includes: (i) acid forms,such as “A-type”, “B-type”, or “AB-type” acid forms; (ii) salts of suchacid forms, such as Na⁺ or Ca²⁺ salts of such acid forms; and/or (iii)ester forms, such as those formed by hydroxyl-group esterification toform traditional esters, sulphonate esters, and/or phosphate esters;and/or (iv) various stereoisomers. In select embodiments of the presentdisclosure, Δ⁸-THC may have the following structural formula:

In the context of the present disclosure, the relative quantities ofΔ⁸-THC and Δ⁹-THC in a particular composition may be expressed as aratio—Δ⁸-THC:Δ⁹-THC. Those skilled in the art will recognize that avariety of analytical methods may be used to determine such ratios, andthe protocols required to implement any such method are within thepurview of those skilled in the art. By way of non-limiting example,Δ⁸-THC:Δ⁹-THC ratios may be determined by diode-array-detector highpressure liquid chromatography, UV-detector high pressure liquidchromatography, nuclear magnetic resonance spectroscopy, massspectroscopy, flame-ionization gas chromatography, gaschromatograph-mass spectroscopy, or combinations thereof. In selectembodiments of the present disclosure, the compositions provided by themethods of the present disclosure have Δ⁸-THC:Δ⁹-THC ratios of greaterthan 1.0:1.0, meaning the quantity of Δ⁸-THC in the composition isgreater than the quantity of Δ⁹-THC in the composition. For example, thecompositions provided by the methods of the present disclosure may haveΔ⁸-THC:Δ⁹-THC ratios of: (i) greater than about 2.0:1.0; (ii) greaterthan about 3.0:1.0; (iii) greater than about 5.0:1.0; (iv) greater thanabout 10.0:1.0; (v) greater than about 15.0:1.0; (vi) greater than about20.0:1.0; (vii) greater than about 50.0:1.0; and (viii) greater thanabout 100.0:1.0.

In the context of the present disclosure, converting CBD into“primarily” Δ⁸-THC refers to converting CBD into exclusively Δ⁸-THC orinto a composition in which Δ⁸-THC is present to a greater extent thanany other reaction product. In select embodiments of the presentdisclosure, converting CBD into “primarily” Δ⁸-THC may yield a productmixture which is at least: (i) 50% Δ⁸-THC on a molar basis; (ii) 60%Δ⁸-THC on a molar basis; (iii) 70% Δ⁸-THC on a molar basis; (iv) 80%Δ⁸-THC on a molar basis; (v) 90% Δ⁸-THC on a molar basis; or (vi) 95%Δ⁸-THC on a molar basis. Importantly converting CBD into a compositionin which Δ⁸-THC is the primary product does not necessarily imply thatCBD is the most prevalent component of a reaction composition, as otherconstituents derived from the starting material may be more prevalent.For example, Δ⁸-THC may be the primary product in a reaction mixturethat includes primarily unreacted CBD.

In the context of the present disclosure, a Lewis-acid heterogeneousreagent is one which: (i) comprises one or more sites that are capableof accepting an electron pair from an electron pair donor; and (ii) issubstantially not mono-phasic with the reagent (i.e. CBD). Likewise, inthe context of the present disclosure, a Brønsted-acid heterogeneousreagent is one which: (i) comprises one or more sites that are capableof donating a proton to a proton-acceptor; and (ii) is substantially notmono-phasic with the starting material and/or provides an interfacewhere one or more chemical reaction takes place. Importantly, the term“reagent” is used in the present disclosure to encompass bothreactant-type reactivity (i.e. wherein the reagent is at least partlyconsumed as reactant is converted to product) and catalyst-typereactivity (i.e. wherein the reagent is not substantially consumed asreactant is converted to product).

In the context of the present disclosure, the acidity of a Lewis-acidheterogeneous reagent and/or a Brønsted-acid heterogeneous reagent maybe characterized by a variety of parameters, non-limiting examples ofwhich are summarized in the following paragraphs.

As will be appreciated by those skilled in the art who have benefittedfrom the teachings of the present disclosure, determining the acidity ofheterogeneous solid acids may be significantly more challenging thanmeasuring the acidity of homogenous acids due to the complex molecularstructure of heterogeneous solid acids. The Hammett acidity function(H₀) has been applied over the last 60 years to characterize the acidityof solid acids in non-aqueous solutions. This method utilizes organicindicator bases, known as Hammett indicators, which coordinate to theaccessible acidic sites of the solid acid upon protonation. Typically, acolor change is observed during titration with an additional organicbase (e.g. n-butylamine), which is measured by UV-visible spectroscopyto quantify acidity. Multiple Hammett indicators with pKa values rangingfrom +6.8 (e.g. neutral red) to −8.2 (e.g. anthraquinone) are testedwith a given solid acid to determine the quantity and strength of acidicsites, which is typically expressed in mmol per gram of solid acid foreach indicator. Hammett acidity values may not provide a completecharacterization of acidity. For example, accurate measurement ofacidity may rely on the ability of the Hammett indicator to access theinterior acidic sites within the solid acid. Some solid acids may havepore sizes that permit the passage of small molecules but prevent largermolecules from accessing the interior of the acid. H-ZSM-5 may be arepresentative example, wherein larger Hammett indicators such asanthraquinone may not be able to access interior acidic sites, which maylead to an incomplete measure of its total acidity.

Temperature-Programmed Desorption (TPD) is an alternate technique forcharacterizing the acidity of heterogeneous solid acids. This techniquetypically utilizes an organic base with small molecular size (e.g.ammonia, pyridine, n-propylamine), which may react with the acid siteson the exterior and interior of the solid acid in a closed system. Afterthe solid acid is substantially saturated with organic base, thetemperature is increased and the change in organic base concentration ismonitored gravimetrically, volumetrically, by gas chromatography, or bymass spectrometry. The amount of organic base desorbing from the solidacid above some characteristic temperature may be interpreted as theacid-site concentration. TPD is often considered more representative oftotal acidity for solid acids compared to the Hammett acidity function,because the selected organic base is small enough to bind to acidicsites on the interior of the solid acid.

In select embodiments of the present disclosure, TPD values are reportedwith respect to ammonia. Those skilled in the art who have benefitedfrom the teachings of the present disclosure will appreciate thatammonia may have the potential disadvantage of overestimating acidity,because its small molecular size enables access to acidic sites on theinterior of the solid acid that are not accessible to typical organicsubstrates being employed for chemical reactions (i.e. ammonia may fitinto pores that CBD cannot). Despite this disadvantage, TPD with ammoniais still considered a useful technique to compare total acidity ofheterogeneous solid acids (larger NH₃ absorption values correlate withstronger acidity).

Another commonly used method for characterizing the acidity ofheterogeneous solid acids is microcalorimetry. In this technique, theheat of adsorption is measured when acidic sites on the solid acid areneutralized by addition of a base. The measured heat of adsorption isused to characterize the strength of Brønsted-acid sites (the larger theheat of adsorption, the stronger the acidic site, such that morenegative values correlate with stronger acidity).

Microcalorimetry may provide the advantage of being a more direct methodfor the determination of acid strength when compared to TPD. However,the nature of the acidic sites cannot be determined by calorimetryalone, because adsorption may occur at Brønsted sites, Lewis sites, or acombination thereof. Further, experimentally determined heats ofadsorption may be inconsistent in the literature for a givenheterogeneous acid. For example, ΔH_(0ads) NH₃ values between about 100kJ/mol and about 200 kJ/mol have been reported for H-ZSM-5. Thus, heatsof adsorption determined by microcalorimetry may be best interpreted incombination with other acidity characterization methods such as TPD toproperly characterize the acidity of solid heterogeneous acids.

Non-limiting examples of: (i) Hammett acidity values; (ii) TPD valueswith reference to ammonia; and (iii) microcalorimetry values withreference to ammonia, for a selection of Lewis-acidic heterogeneousreagents in accordance with the present disclosure are set out in Table1.

TABLE 1 Non-limiting examples of: (i) Hammett acidity values; (ii) TPDvalues with reference to ammonia; and (iii) microcalorimetry values withreference to ammonia. TPD ΔH⁰ _(ads) Acid Hammett Value NH₃ NH₃ ReagentClassification (H₀) (mmol/g) (kJ/mol) Amberlyst-35 Ion-exchange −5.65.2^(])  −117 resin Amberlyst-15 Ion-exchange −4.6 4.6  −116 resinH-ZSM-5 Microporous −5.6 < H₀ < −3.0 1.0^(])  −145 aluminosilicate(zeolite) H-Beta Microporous —.  0.65 −120 aluminosilicate (zeolite)Al-MCM-41 Mesoporous —.  0.26 —. aluminosilicate Montmoril-Phyllosilicate −1.5 < H₀ < +3.2 0.18 —. lonite (K30) (clay)

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent may have a Hammett-acidity value (H_(o)) ofbetween about −8.0 and about 0.0. For example, the Lewis-acidicheterogeneous reagent may have a Hammett-acidity value (H_(o)) ofbetween: (i) about −8.0 and about −7.0; (ii) about −7.0 and about −6.0;(iii) about −6.0 and about −5.0; (iv) about −5.0 and about −4.0; (v)about −4.0 and about −3.0; (vi) about −3.0 and about −2.0; (vii) about−2.0 and about −1.0; or (viii) about −1.0 and about 0.

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent may have a temperature-programmed desorption valueof between about 7.5 and about 0.0 as determined with reference toammonia (TPD_(NH3)). For example, the Lewis-acidic heterogeneous reagentmay have a temperature-programmed desorption value of between: (i) about7.5 and about 6.5 as determined with reference to ammonia (TPD_(NH3));(ii) about 6.5 and about 5.5 as determined with reference to ammonia(TPD_(NH3)); (iii) about 5.5 and about 4.5 as determined with referenceto ammonia (TPD_(NH3)); (iv) about 4.5 and about 3.5 as determined withreference to ammonia (TPD_(NH3)); (v) about 3.5 and about 2.5 asdetermined with reference to ammonia (TPD_(NH3)); (vi) about 2.5 andabout 1.5 as determined with reference to ammonia (TPD_(NH3)); (vii)about 1.5 and about 0.5 as determined with reference to ammonia(TPD_(NH3)); or (viii) about 0.5 and about 0.0 as determined withreference to ammonia (TPD_(NH3)).

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent may have a heat of absorption value of betweenabout −165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)). For example, the Lewis-acidic heterogeneous reagent mayhave a heat of absorption value of between: (i) about −165 and about−150 as determined with reference to ammonia (ΔH°_(ads NH3)); (ii) about−150 and about −135 as determined with reference to ammonia(ΔH°_(ads NH3)); (iii) about −135 and about −120 as determined withreference to ammonia (ΔH°_(ads NH3)); (iv) about −120 and about −105 asdetermined with reference to ammonia (ΔH°_(ads NH3)); or (v) about −105and about −100 as determined with reference to ammonia (ΔH°_(ads NH3)).

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent may comprise an ion-exchange resin, a microporoussilicate such as a zeolite (natural or synthetic), a mesoporous silicate(natural or synthetic) and/or a phyllosilicate (such asmontmorillonite).

Lewis-acidic heterogeneous reagents that comprise an ion-exchange resinmay comprise, for example, Amberlyst polymeric resins (also commonlyreferred to as “Amberlite” resins). Amberlyst polymeric resins includebut are not limited to Amberlyst-15, 16, 31, 33, 35, 36, 39, 46, 70,CH10, CH28, CH43, M-31, wet forms, dry forms, macroreticular forms, gelforms, H⁺ forms, Na⁺ forms, or combinations thereof). In selectembodiments of the present disclosure, the Lewis-acidic heterogeneousreagent may comprise an Amberlyst resin that has a surface area ofbetween about 20 m²/g and about 80 m²/g. In select embodiments of thepresent disclosure, the Lewis-acidic heterogeneous reagent may comprisean Amberlyst resin that has an average pore diameter of between about100 Å and about 500 Å. In select embodiments of the present disclosure,the Lewis-acidic heterogeneous reagent may comprise Amberlyst-15.Amberlyst-15 is a styrene-divinylbenzene-based polymer with sulfonicacid functional groups linked to the polymer backbone. Amberlyst-15 mayhave the following structural formula:

Lewis-acidic heterogeneous reagents that comprise an ion-exchange resinmay comprise, for example, Nafion polymeric resins. Nafion polymericresins may include but are not limited to Nafion-NR50, N115, N117, N324,N424, N1110, SAC-13, powder forms, resin forms, membrane forms, aqueousforms, dispersion forms, composite forms, H⁺ forms, Na⁺ forms, orcombinations thereof.

Lewis-acidic heterogeneous reagents that comprise microporous silicates(e.g. zeolites) may comprise, for example, natural and syntheticzeolites. Lewis-acidic heterogeneous reagents that comprise mesoporoussilicates may comprise, for example, Al-MCM-41 and/or MCM-41.Lewis-acidic heterogeneous reagents that comprise phyllosilicates maycomprise, for example, montmorillonite. A commonality amongst thesematerials is that they are all silicates. Silicates may include but arenot limited to Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11,ZSM-22, ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6,FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X,Linde type Y, Faujasite, USY, Mordenite, Ferrierite, MontmorilloniteK10, K30, KSF, Clayzic, bentonite, H⁺ forms, Na⁺ forms, or combinationsthereof. Zeolites are commonly used as adsorbents and catalysts (e.g. influid catalytic cracking and hydrocracking in the petrochemicalindustry). Although zeolites are abundant in nature, the zeolites usedfor commercial and industrial processes are often made synthetically.Their structural framework consists of SiO₄ and AlO₄ ⁻ tetrahedra, whichare combined in specific ratios with an amine or tetraalkylammonium salt“template” to give a zeolite with unique acidity, shape and pore size.The Lewis and/or Brønsted-Lowry acidity of zeolites can typically bemodified using two approaches. One approach involves adjusting the Si/Alratio. Since an AlO₄ ⁻ moiety is unstable when attached to another AlO₄⁻ unit, it is necessary for them to be separated by at least one SiO₄unit. The strength of the individual acidic sites may increase as theAlO₄ ⁻ units are further separated Another approach involves cationexchange. Since zeolites contain charged AlO₄ ⁻ species, anextra-framework cation such as Na⁺ is required to maintainelectroneutrality. The extra-framework cations can be replaced withprotons to generate the “H-form” zeolite, which has stronger Brønstedacidity than its metal cation counterpart.

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent may comprise “H⁺-form” zeolites “Na⁺-form”zeolites, and/or a suitable mesoporous material. By way of non-limitingexample, the acidic heterogeneous reagent may comprise Al-MCM-41,MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11, ZSM-22, ZSM-23, ZSM-35,SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6, FDU-12, Beta, X-type,Y-type, Linde type A, Linde type L, Linde type X, Linde type Y,Faujasite, USY, Mordenite, Ferrierite, montmorillonite, bentonite, orcombinations thereof. Suitable mesoporous materials and zeolites mayhave a pore diameter ranging from about 0.1 nm to about 100 nm, particlesizes ranging from about 0.1 μm to about 50 μm, Si/Al ratio ranging from5-1500, and any of the following cations: H⁺, Na⁺, K⁺, NH₄ ⁺, Rb⁺, Cs⁺,Ag⁺. Furthermore, suitable zeolites may have frameworks that aresubstituted with or coordinated to other atoms including, for example,titanium, copper, iron, cobalt, manganese, chromium, zinc, tin,zirconium, and gallium.

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent is H-ZSM-5 (P-38 (Si/Al=38), H⁺ form, ˜5 angstrompore size, 2 μm particle size), Na-ZSM-5 (P-38 (Si/Al=38), Na⁺ form, ˜5angstrom pore size, 2 μm particle size), Al-MCM-41 (aluminum-doped MobilComposition of Matter No. 41; e.g., P-25 (Si/Al=25), 2.7 nm porediameter), or combinations thereof.

In select embodiments of the present disclosure, the Lewis-acidicheterogeneous reagent is Al-MCM-41 and the CBD is comprised in a CBDdistillate. In these embodiments, the reaction conditions may be chosento selectively form Δ⁸-THC.

In select embodiments of the present disclosure, CBD is contacted with aLewis-acidic reagent in a protic-solvent system. By way of non-limitingexample a protic-solvent system may comprise methanol, ethanol,1-propanol, 2-propanol, 1-butanol, 2-butanol, water, acetic acid, formicacid, 3-methyl-1-butanol, 2-methyl-1-propanol, 1-pentanol, nitromethane,or a combination thereof.

In select embodiments of the present disclosure, CBD is contacted with aLewis-acidic reagent in an aprotic-solvent system. By way ofnon-limiting example an aprotic-solvent system may comprise dimethylsulfoxide, ethyl acetate, dichloromethane, chloroform, toluene, pentane,heptane, hexane, diethyl ether, tert-butyl methyl ether,tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide,N-methylpyrrolidone, anisole, butyl acetate, cumene, ethyl formate,isobutyl acetate, isopropyl acetate, methyl acetate, methylethylketone,methylisobutylketone, propyl acetate, cyclohexane, para-xylene,meta-xylene, ortho-xylene, 1,2-dichloroethane, or a combination thereof.As will be appreciated by those skilled in the art who have benefittedfrom the present disclosure, aprotic solvent systems may comprise smallamounts of protic species, the quantities of which may be influenced bythe extent to which drying and/or degassing procedures are employed.

In select embodiments, the methods of the present disclosure may beconducted in the presence of a class III solvent. Heptane, ethanol, andcombinations thereof are non-limiting examples of class III solvents.

In select embodiments of the present disclosure, CBD is contacted with aLewis-acidic reagent under neat reaction conditions. As will beappreciated by those skilled in the art who have benefitted from thepresent disclosure, neat reaction conditions are substantially free ofsolvent.

In select embodiments of the present disclosure, CBD is contacted with aLewis-acidic reagent under reaction conditions characterized by: (i) areaction temperature that is greater than a threshold reactiontemperature for the particular Lewis-acidic heterogeneous reagent andthe particular solvent system; and (ii) a reaction time that is greaterthan a threshold reaction time for the particular Lewis-acidicheterogeneous reagent, the particular solvent system, and the particularreaction temperature. As evidenced by the examples of the presentdisclosure, the acidity of the Lewis-acidic heterogeneous reagent andthe characteristics of the solvent system impact the thresholdreaction-temperature and the threshold reaction time. Without beingbound to any particular theory, the examples of the present disclosureappear to indicate that aprotic solvent-systems, increased acidity,increased reaction temperatures, and/or increased reaction times appearto favor Δ⁸-THC formation over Δ⁹-THC formation. Importantly, thesereaction parameters appear to be dependent variables in that alteringone may impact the others. As such, each reaction temperature may beconsidered in reference to a threshold reaction temperature for theparticular Lewis-acidic heterogeneous reagent, the particular solventsystem, and the particular reaction time associated with the reaction.Likewise, each reaction time in the present disclosure may be consideredin reference to a threshold reaction time for the particularLewis-acidic heterogeneous reagent, the particular solvent system, andthe particular reaction temperature. With respect to reactiontemperatures, by way of non-limiting example, methods of the presentdisclosure may involve reaction temperatures ranging from about 0° C. toabout 200° C. For example, methods of the present disclosure may involvereaction temperatures between: (i) about 5° C. and about 15° C.; (ii)about 15° C. and about 25° C.; (iii) about 25° C. and about 35° C.; (iv)about 35° C. and about 45° C.; (v) about 45° C. and about 55° C.; (vi)about 55° C. and about 65° C.; (vii) about 65° C. and about 75° C.;(viii) about 75° C. and about 85° C.; (ix) about 85° C. and about 95°C.; (x) about 95° C. and about 105° C.; (xi) about 105° C. and about115° C.; or a combination thereof. Of course, the reaction temperaturemay be varied over the course of the reaction while still beingcharacterized the one or more of the foregoing reaction temperatures.With respect to reaction times, by way of non-limiting example, methodsof the present disclosure may involve reaction temperatures ranging fromabout 30 minutes to about 85 hours. For example, methods of the presentdisclosure may involve reaction times between: (i) 30 minutes and about1 hour; (ii) about 1 hour and about 5 hours; (iii) about 5 hours andabout 10 hours; (iv) about 10 hours and 25 hours; (v) about 25 hours andabout 40 hours; (vi) about 40 hours and about 55 hours; (vii) about 55hours and about 70 hours; or (viii) about 70 hours and about 85 hours.

In select embodiments, methods of the present disclosure may involvereactant (i.e. CBD) concentrations ranging from about 0.001 M to about 2M. For example methods of the present disclosure may involve reactantconcentrations of: (i) between about 0.01 M and about 0.1 M; (ii)between about 0.1 M and about 0.5 M; (iii) between about 0.5 M and about1.0 M; (iv) between about 1.0 M and about 1.5 M; or (v) between about1.5 M and about 2.0 M.

In select embodiments, methods of the present disclosure may involveLewis-acidic heterogeneous reagent loadings ranges from about 0.1 molarequivalents to about 100 molar equivalents relative to the reactant(i.e. CBD). For example methods of the present disclosure may involveLewis-acidic heterogeneous reagent loadings of: (i) between about 0.1molar equivalents to about 1.0 molar equivalents, relative to thereactant; (ii) 0.1.0 molar equivalents to about 5.0 molar equivalents,relative to the reactant; (iii) 5.0 molar equivalents to about 10.0molar equivalents, relative to the reactant; (iv) 10.0 molar equivalentsto about 50.0 molar equivalents, relative to the reactant; or (v) 50.0molar equivalents to about 100.0 molar equivalents, relative to thereactant.

In select embodiments, the methods of the present disclosure may producean amount of exo-tetrahydrocannabinol (exo-THC). In select embodiments,the amount of exo-THC is detectable by HPLC. In select embodiments, theformation of exo-THC may be directly related to the Brønsted-acidity ofthe catalyst. Exo-THC may have the following structure:

In select embodiments, the methods of the present disclosure may furthercomprise a filtering step. By way of non-limiting example the filteringstep may employ a fritted Buchner filtering funnel. Suitable filteringapparatus and protocols are within the purview of those skilled in theart.

In select embodiments, the methods of the present disclosure may furthercomprise a solvent evaporation step, and the solvent evaporation stepmay be executed under reduced pressure (i.e. in vacuo) for example witha rotary evaporator. Suitable evaporating apparatus and protocols arewithin the purview of those skilled in the art.

In select embodiments, the methods of the present disclosure may furthercomprise a step of distillation. Without being bound by any particulartheory, distillation may remove impurities and result in a compositioncomprising a total cannabinoid content about equal to the totalcannabinoid content prior to undergoing the methods disclosed herein.Suitable distillation apparatus and protocols are within the purview ofthose skilled in the art.

Exemplary Embodiments

The following are non-limiting and exemplary embodiments of the presentdisclosure:

(1) A method for converting cannabidiol (CBD) into a compositioncomprising Δ⁸-tetrahydrocannabinol (Δ⁸-THC) and Δ⁹-tetrahydrocannabinol(Δ⁹-THC), wherein the composition has a Δ⁸-THC:Δ⁹-THC ratio that isgreater than 1.0:1.0, the method comprising contacting the CBD with aLewis-acidic heterogeneous reagent under reaction conditions comprising:(i) an aprotic-solvent system; (ii) a reaction temperature that isgreater than a threshold reaction temperature for the Lewis-acidicheterogeneous reagent and the aprotic-solvent system; and (iii) areaction time that is greater than a threshold reaction time for theLewis-acidic heterogeneous reagent, the aprotic-solvent system, and thereaction temperature.

(2) The method of (1), wherein the Lewis-acidic heterogeneous reagent isa Brønsted-acidic heterogeneous reagent.

(3) The method of (1) or (2), wherein the Lewis-acidic heterogeneousreagent has a Hammett-acidity value (H_(o)) of between about −8.0 andabout 0.0.

(4) The method of any one of (1) to (3), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(5) The method of any one of (1) to (4), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(6) The method of (1), wherein the Lewis-acidic heterogeneous reagentcomprises an ion-exchange resin, a microporous silicate, a mesoporoussilicate, a phyllosilicate, or a combination thereof.

(7) The method of (6), wherein the ion-exchange resin is an Amberlystpolymeric resin.

(8) The method of (7), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(9) The method of (7) or (8), wherein the Amberlyst polymeric resincomprises Amberlyst 15.

(10) The method of (6), wherein the ion-exchange resin is a Nafionpolymeric resin.

(11) The method of (10), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(12) The method of (6), wherein the Lewis-acidic heterogeneous reagentis Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11, ZSM-22,ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6, FDU-12,Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Lindetype Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF,Clayzic, bentonite, or a combination thereof.

(13) The method of (12), wherein the acidic heterogeneous reagent has apore diameter of between about 0.1 nm and about 100 nm, a particle sizeof between about 0.1 μm and about 50 μm, a Si/Al ratio of between about5 and about 1500, or a combination thereof.

(14) The method of (12) or (13), wherein the Lewis-acidic heterogeneousreagent is H-ZSM-5, with a Si/Al ratio of about 38, a pore size of about5 Å, and a particle size of about 2 μm.

(15) The method of (12) or (13), wherein the Lewis-acidic heterogeneousreagent is Na-ZSM-5, with a Si/Al ratio of about 38, a pore size ofabout 5 Å, and a particle size of about 2 μm.

(16) The method of (12) or (13), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41 with a Si/Al ratio of about 25, and a pore diameterof about 2.7 nm.

(17) The method of any one of (1) to (16), wherein the aprotic-solventsystem comprises a class III solvent.

(18) The method of (17), wherein the class III solvent is heptane.

(19) The method of any one of (1) to (18), wherein prior to beingconverted to the composition comprising the Δ⁸-THC and the Δ⁹-THC, theCBD is dissolved in the aprotic-solvent system at a concentrationbetween about 0.001 M and about 2 M.

(20) The method of any one of (1) to (19), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(21) The method of any one of (1) to (20), wherein the thresholdreaction time is between about 10 minutes and about 72 hours.

(22) The method of any one of (1) to (21), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(23) The method of any one of (1) to (22), further comprising isolatingthe composition from the acidic heterogeneous reagent by a solid-liquidseparation technique.

(24) The method of (23), wherein the solid-liquid separation techniquecomprises filtration, decantation, centrifugation, or a combinationthereof.

(25) The method of any one of (1) to (24), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(26) The method of (25), wherein the extract is a crude extract fromhemp.

(27) The method of any one of (1) to (26), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 3.0:1.0.

(28) The method of any one of (1) to (26), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 6.0:1.0.

(29) The method of any one of (1) to (26), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 20.0:1.0.

(30) A method for converting cannabidiol (CBD) intoΔ⁸-tetrahydrocannabinol (Δ⁸-THC), the method comprising contacting theCBD with a Lewis-acidic heterogeneous reagent under reaction conditionscomprising: (i) an aprotic-solvent system; (ii) a reaction temperaturethat is greater than a threshold reaction temperature for theLewis-acidic heterogeneous reagent and the aprotic-solvent system; and(iii) a reaction time that is greater than a threshold reaction time forthe Lewis-acidic heterogeneous reagent, the aprotic-solvent system, andthe reaction temperature.

(31) The method of (30), wherein the Lewis-acidic heterogeneous reagentis a Brønsted-acidic heterogeneous reagent.

(32) The method of (30) or (31), wherein the Lewis-acidic heterogeneousreagent has a Hammett-acidity value (H_(o)) of between about −8.0 andabout 0.0.

(33) The method of any one of (30) to (32), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(34) The method of any one of (30) to (33), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(35) The method of (30), wherein the Lewis-acidic heterogeneous reagentcomprises an ion-exchange resin, a microporous silicate, a mesoporoussilicate, a phyllosilicate, or a combination thereof.

(36) The method of (35), wherein the ion-exchange resin is an Amberlystpolymeric resin.

(37) The method of (36), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(38) The method of (36) or (37), wherein the Amberlyst polymeric resincomprises Amberlyst 15.

(39) The method of (35), wherein the ion-exchange resin is a Nafionpolymeric resin.

(40) The method of (39), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(41) The method of (35), wherein the Lewis-acidic heterogeneous reagentis Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11, ZSM-22,ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6, FDU-12,Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Lindetype Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF,Clayzic, bentonite, or a combination thereof.

(42) The method of (41), wherein the acidic heterogeneous reagent has apore diameter of between about 0.1 nm and about 100 nm, a particle sizeof between about 0.1 μm and about 50 μm, a Si/Al ratio of between about5 and about 1500, or a combination thereof.

(43) The method of (41) or (42), wherein the Lewis-acidic heterogeneousreagent is H-ZSM-5, with a Si/Al ratio of about 38, a pore size of about5 Å, and a particle size of about 2 μm.

(44) The method of (41) or (42), wherein the Lewis-acidic heterogeneousreagent is Na-ZSM-5, with a Si/Al ratio of about 38, a pore size ofabout 5 Å, and a particle size of about 2 μm.

(45) The method of (41) or (42), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41 with a Si/Al ratio of about 25, and a pore diameterof about 2.36 nm.

(46) The method of any one of (30) to (35), wherein the aprotic-solventsystem comprises a class III solvent.

(47) The method of (46), wherein the class III solvent is heptane.

(48) The method of any one of (30) to (47), wherein prior to beingconverted to the Δ⁸-THC, the CBD is dissolved in the aprotic-solventsystem at a concentration between about 0.001 M and about 2 M.

(49) The method of any one of (30) to (48), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(50) The method of any one of (30) to (49), wherein the thresholdreaction time is between about 10 minutes and about 36 hours.

(51) The method of any one of (30) to (50), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(52) The method of any one of (30) to (51), further comprising isolatingthe composition from the acidic heterogeneous reagent by a solid-liquidseparation technique.

(53) The method of (52), wherein the solid-liquid separation techniquecomprises filtration, decantation, centrifugation, or a combinationthereof.

(54) The method of any one of (30) to (53), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(55) The method of (54), wherein the extract is a crude extract fromhemp.

(56) A method for converting cannabidiol (CBD) into a compositioncomprising Δ⁸-tetrahydrocannabinol (Δ⁸-THC) and Δ⁹-tetrahydrocannabinol(Δ⁹-THC), wherein the composition has a Δ⁸-THC:Δ⁹-THC ratio that isgreater than 1.0:1.0, the method comprising contacting the CBD with aLewis-acidic heterogeneous reagent under neat reaction conditionscomprising: (i) a reaction temperature that is greater than a thresholdreaction temperature for the Lewis-acidic heterogeneous reagent; and(ii) a reaction time that is greater than a threshold reaction time forthe Lewis-acidic heterogeneous reagent and the reaction temperature.

(57) The method of (56), wherein the Lewis-acidic heterogeneous reagentis a Brønsted-acidic heterogeneous reagent.

(58) The method of (56) or (57), wherein the Lewis-acidic heterogeneousreagent has a Hammett-acidity value (H_(o)) of between about −8.0 andabout 0.0.

(59) The method of any one of (56) to (58), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(60) The method of any one of (56) to (59), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(61) The method of (56), wherein the Lewis-acidic heterogeneous reagentcomprises ion-exchange resin, a microporous silicate, a mesoporoussilicate, a phyllosilicate, or a combination thereof.

(62) The method of (61), wherein the ion-exchange resin is an Amberlystpolymeric resin.

(63) The method of (62), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(64) The method of (62) or (63), wherein the Amberlyst polymeric resincomprises Amberlyst 15.

(65) The method of (61), wherein the ion-exchange resin is a Nafionpolymeric resin.

(66) The method of (65), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(67) The method of (61), wherein the Lewis-acidic heterogeneous reagentis Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11, ZSM-22,ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6, FDU-12,Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Lindetype Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF,Clayzic, bentonite, or a combination thereof.

(68) The method of (67), wherein the acidic heterogeneous reagent has apore diameter of between about 0.1 nm and about 100 nm, a particle sizeof between about 0.1 μm and about 50 μm, a Si/Al ratio of between about5 and about 1500, or a combination thereof.

(69) The method of (67) or (68), wherein the Lewis-acidic heterogeneousreagent is H-ZSM-5, with a Si/Al ratio of about 38, a pore size of about5 Å, and a particle size of about 2 μm.

(70) The method of (67) or (68), wherein the Lewis-acidic heterogeneousreagent is Na-ZSM-5, with a Si/Al ratio of about 38, a pore size ofabout 5 Å, and a particle size of about 2 μm.

(71) The method of (67) or (68), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41 with a Si/Al ratio of about 25, and a pore diameterof about 2.7 nm.

(72) The method of any one of (56) to (71), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(73) The method of any one of (56) to (72), wherein the thresholdreaction time is between about 10 minutes and about 72 hours.

(74) The method of any one of (56) to (73), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(75) The method of any one of (56) to (74), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(76) The method of (75), wherein the extract is a crude extract fromhemp.

(77) The method of any one of (56) to (76), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 3.0:1.0.

(78) The method of any one of (56) to (76), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 6.0:1.0.

(79) The method of any one of (56) to (76), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 20.0:1.0.

(80) A method for converting cannabidiol (CBD) intoΔ⁸-tetrahydrocannabinol (Δ⁸-THC), the method comprising contacting theCBD with a Lewis-acidic heterogeneous reagent under neat reactionconditions comprising: (i) a reaction temperature that is greater than athreshold reaction temperature for the Lewis-acidic heterogeneousreagent; and (ii) a reaction time that is greater than a thresholdreaction time for the Lewis-acidic heterogeneous reagent and thereaction temperature.

(81) The method of (80), wherein the Lewis-acidic heterogeneous reagentis a Brønsted-acidic heterogeneous reagent.

(82) The method of (80) or (81), wherein the Lewis-acidic heterogeneousreagent has a Hammett-acidity value (H_(o)) of between about −8.0 andabout 0.0.

(83) The method of any one of (80) to (82), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(84) The method of any one of (80) to (83), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(85) The method of (80), wherein the Lewis-acidic heterogeneous reagentcomprises an ion-exchange resin, a microporous silicate, a mesoporoussilicate, a phyllosilicate, or a combination thereof.

(86) The method of (85), wherein the ion-exchange resin is an Amberlystpolymeric resin.

(87) The method of (86), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(88) The method of (86) or (87), wherein the Amberlyst polymeric resincomprises Amberlyst 15.

(89) The method of (85), wherein the ion-exchange resin is a Nafionpolymeric resin.

(90) The method of (89), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(91) The method of (85), wherein the Lewis-acidic heterogeneous reagentis Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11, ZSM-22,ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6, FDU-12,Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X, Lindetype Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10, K30, KSF,Clayzic, bentonite, or a combination thereof.

(92) The method of (91), wherein the acidic heterogeneous reagent has apore diameter of between about 0.1 nm and about 100 nm, a particle sizeof between about 0.1 μm and about 50 μm, a Si/Al ratio of between about5 and about 1500, or a combination thereof.

(93) The method of (91) or (92), wherein the Lewis-acidic heterogeneousreagent is H-ZSM-5, with a Si/Al ratio of about 38, a pore size of about5 Å, and a particle size of about 2 μm.

(94) The method of (91) or (92), wherein the Lewis-acidic heterogeneousreagent is Na-ZSM-5, with a Si/Al ratio of about 38, a pore size ofabout 5 Å, and a particle size of about 2 μm.

(95) The method of (91) or (92), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41 with a Si/Al ratio of about 25, and a pore diameterof about 2.7 nm.

(96) The method of any one of (80) to (95), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(97) The method of any one of (80) to (96), wherein the thresholdreaction time is between about 10 minutes and about 72 hours.

(98) The method of any one of (80) to (97), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(99) The method of any one of (80) to (98), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(100) The method of (99), wherein the extract is a crude extract fromhemp.

(101) A method for converting CBD into a composition comprising Δ⁸-THCand Δ⁹-THC, wherein the composition has a Δ⁸-THC:Δ⁹-THC ratio that isgreater than 1.0:1.0, the method comprising contacting the CBD with aLewis-acidic heterogeneous reagent under reaction conditions comprising:(i) a protic-solvent system; (ii) a reaction temperature that is greaterthan a threshold reaction temperature for the Lewis-acidic heterogeneousreagent and the protic-solvent system; and (iii) a reaction time that isgreater than a threshold reaction time for the Lewis-acidicheterogeneous reagent, the protic-solvent system, and the reactiontemperature.

(102) The method of (101), wherein the Lewis-acidic heterogeneousreagent is a Brønsted-acidic heterogeneous reagent.

(103) The method of (101) or (102), wherein the Lewis-acidicheterogeneous reagent has a Hammett-acidity value (H_(o)) of betweenabout −8.0 and about 0.0.

(104) The method of any one of (101) to (103), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(105) The method of any one of (101) to (104), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(106) The method of (101), wherein the Lewis-acidic heterogeneousreagent comprises an ion-exchange resin, a microporous silicate, amesoporous silicate, a phyllosilicate, or a combination thereof.

(107) The method of (106), wherein the ion-exchange resin is anAmberlyst polymeric resin.

(108) The method of (107), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(109) The method of (107) or (108), wherein the Amberlyst polymericresin comprises Amberlyst 15.

(110) The method of (106), wherein the ion-exchange resin is a Nafionpolymeric resin.

(111) The method of (110), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(112) The method of (106), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11,ZSM-22, ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6,FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X,Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10,K30, KSF, Clayzic, bentonite, or a combination thereof.

(113) The method of (112), wherein the acidic heterogeneous reagent hasa pore diameter of between about 0.1 nm and about 100 nm, a particlesize of between about 0.1 μm and about 50 μm, a Si/Al ratio of betweenabout 5 and about 1500, or a combination thereof.

(114) The method of (112) or (113), wherein the Lewis-acidicheterogeneous reagent is H-ZSM-5, with a Si/Al ratio of about 38, a poresize of about 5 Å, and a particle size of about 2 μm.

(115) The method of (112) or (113), wherein the Lewis-acidicheterogeneous reagent is Na-ZSM-5, with a Si/Al ratio of about 38, apore size of about 5 Å, and a particle size of about 2 μm.

(116) The method of (112) or (113), wherein the Lewis-acidicheterogeneous reagent is Al-MCM-41 with a Si/Al ratio of about 25, and apore diameter of about 2.7 nm.

(117) The method of any one of (101) to (116), wherein theprotic-solvent system comprises a class III solvent.

(118) The method of (117), wherein the class III solvent is ethanol.

(119) The method of any one of (101) to (118), wherein prior to beingconverted to the composition comprising the Δ⁸-THC and the Δ⁹-THC, theCBD is dissolved in the protic-solvent system at a concentration betweenabout 0.001 M and about 2 M.

(120) The method of any one of (101) to (119), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(121) The method of any one of (101) to (120), wherein the thresholdreaction time is between about 10 minutes and about 72 hours.

(122) The method of any one of (101) to (121), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(123) The method of any one of (101) to (122), further comprisingisolating the composition from the acidic heterogeneous reagent by asolid-liquid separation technique.

(124) The method of (123), wherein the solid-liquid separation techniquecomprises filtration, decantation, centrifugation, or a combinationthereof.

(125) The method of any one of (101) to (124), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(126) The method of (125), wherein the extract is a crude extract fromhemp.

(127) The method of any one of (101) to (126), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 3.0:1.0.

(128) The method of any one of (101) to (126), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 6.0:1.0.

(129) The method of any one of (101) to (126), wherein the Δ⁸-THC:Δ⁹-THCratio of the composition is greater than about 20.0:1.0.

(130) A method for converting CBD into Δ⁸-THC, the method comprisingcontacting the CBD with a Lewis-acidic heterogeneous reagent underreaction conditions comprising: (i) a protic-solvent system; (ii) areaction temperature that is greater than a threshold reactiontemperature for the Lewis-acidic heterogeneous reagent and theprotic-solvent system; and (iii) a reaction time that is greater than athreshold reaction time for the Lewis-acidic heterogeneous reagent, theprotic-solvent system, and the reaction temperature.

(131) The method of (130), wherein the Lewis-acidic heterogeneousreagent is a Brønsted-acidic heterogeneous reagent.

(132) The method of (130) or (131), wherein the Lewis-acidicheterogeneous reagent has a Hammett-acidity value (H_(o)) of betweenabout −8.0 and about 0.0.

(133) The method of any one of (130) to (132), wherein the Lewis-acidicheterogeneous reagent has a temperature-programmed desorption value ofbetween about 7.5 and about 0.0 as determined with reference to ammonia(TPD_(NH3)).

(134) The method of any one of (130) to (133), wherein the Lewis-acidicheterogeneous reagent has a heat of absorption value of between about−165 and about −100 as determined with reference to ammonia(ΔH°_(ads NH3)).

(135) The method of (1), wherein the Lewis-acidic heterogeneous reagentcomprises an ion-exchange resin, a microporous silicate, a mesoporoussilicate, a phyllosilicate, or a combination thereof.

(136) The method of (135), wherein the ion-exchange resin is anAmberlyst polymeric resin.

(137) The method of (136), wherein the Amberlyst polymeric resin has asurface area of between about 20 m²/g and about 80 m²/g and an averagepore diameter of between about 100 Å and about 500 Å.

(138) The method of (136) or (137), wherein the Amberlyst polymericresin comprises Amberlyst 15.

(139) The method of (135), wherein the ion-exchange resin is a Nafionpolymeric resin.

(140) The method of (139), wherein the Nafion polymeric resin comprisesNR50, N115, N117, N324, N424, N1110, SAC-13, or a combination thereof.

(141) The method of (135), wherein the Lewis-acidic heterogeneousreagent is Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, ZSM-5, ZSM-11,ZSM-22, ZSM-23, ZSM-35, SAPO-11, SAPO-34, SSZ-13, TS-1, KIT-5, KIT-6,FDU-12, Beta, X-type, Y-type, Linde type A, Linde type L, Linde type X,Linde type Y, Faujasite, Mordenite, Ferrierite, Montmorillonite K10,K30, KSF, Clayzic, bentonite, or a combination thereof.

(142) The method of (141), wherein the acidic heterogeneous reagent hasa pore diameter of between about 0.1 nm and about 100 nm, a particlesize of between about 0.1 μm and about 50 μm, a Si/Al ratio of betweenabout 5 and about 1500, or a combination thereof.

(143) The method of (141) or (142), wherein the Lewis-acidicheterogeneous reagent is H-ZSM-5, with a Si/Al ratio of about 38, a poresize of about 5 Å, and a particle size of about 2 μm.

(144) The method of (141) or (142), wherein the Lewis-acidicheterogeneous reagent is Na-ZSM-5, with a Si/Al ratio of about 38, apore size of about 5 Å, and a particle size of about 2 μm.

(145) The method of (141) or (142), wherein the Lewis-acidicheterogeneous reagent is Al-MCM-41 with a Si/Al ratio of about 25, and apore diameter of about 2.7 nm.

(146) The method of any one of (130) to (145), wherein theprotic-solvent system comprises a class III solvent.

(147) The method of (146), wherein the class III solvent is ethanol.

(148) The method of any one of (130) to (147), wherein prior to beingconverted to the Δ⁸-THC, the CBD is dissolved in the protic-solventsystem at a concentration between about 0.001 M and about 2 M.

(149) The method of any one of (130) to (148), wherein the thresholdreaction temperature is between about 20° C. and about 100° C.

(150) The method of any one of (130) to (149), wherein the thresholdreaction time is between about 10 minutes and about 72 hours.

(151) The method of any one of (130) to (150), wherein the Lewis-acidicheterogeneous reagent has a reagent loading between about 0.1 molarequivalents and about 100 molar equivalents relative to the CBD.

(152) The method of any one of 130) to (151), further comprisingisolating the composition from the acidic heterogeneous reagent by asolid-liquid separation technique.

(153) The method of (152), wherein the solid-liquid separation techniquecomprises filtration, decantation, centrifugation, or a combinationthereof.

(154) The method of any one of (130) to (153), wherein the CBD is acomponent of a distillate, an isolate, a concentrate, an extract, or acombination thereof.

(155) The method of (154), wherein the extract is a crude extract fromhemp.

(156) A method for converting CBD into Δ⁸-THC, the method comprisingcontacting the CBD with an ion-exchange resin under reaction conditionscomprising: (i) a class III solvent; (ii) a reaction temperature that isgreater than about 60° C.; and (iii) a reaction time that is greaterthan about 60 minutes.

(157) A method for converting CBD into a composition comprising Δ⁸-THCand Δ⁹-THC, wherein the composition has a Δ⁸-THC:Δ⁹-THC ratio that isgreater than 1.0:1.0, the method comprising contacting the CBD with analuminosilicate-based reagent under reaction conditions comprising: (i)a class III solvent; (ii) a reaction temperature that is greater thanabout 70° C.; and (iii) a reaction time that is greater than about 60minutes.

Examples

EXAMPLE 1: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Amberlyst-15 (100 mg). The reaction was stirred at roomtemperature for 24 hours. The reaction was filtered using a frittedBuchner filtering funnel and then the reaction solvent was evaporated invacuo. Analysis by HPLC showed near complete consumption of CBD (<1%remained) with Δ⁸-THC as the major product (see, TABLE 2 and FIG. 1).

EXAMPLE 2: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Al-MCM-41 (1 g, ACS Material). The reaction was stirred atreflux for 18 hours. The reaction was cooled to room temperature andthen filtered using a fritted Buchner filtering funnel. The reactionsolvent was evaporated in vacuo. Analysis by HPLC showed completeconsumption of CBD with Δ⁸-THC as the major product (see, TABLE 2 andFIG. 2).

EXAMPLE 3: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Amberlyst-15 (500 mg). The reaction was stirred at 60° C. for2 hours. The reaction was cooled to room temperature and then filteredusing a fritted Buchner filtering funnel. The reaction solvent wasevaporated in vacuo. Analysis by HPLC showed near complete consumptionof CBD (<0.2% remained) with Δ⁸-THC as the major product (see, TABLE 2and FIG. 3).

EXAMPLE 4: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Amberlyst-15 (500 mg). The reaction was stirred and heated toreflux for 2 hours. The reaction was cooled to room temperature and thenfiltered using a fritted Buchner filtering funnel. The reaction solventwas evaporated in vacuo. Analysis by HPLC showed complete consumption ofCBD with Δ⁸-THC as the major product (see, TABLE 2 and FIG. 4).

EXAMPLE 5: A mixture of CBD (500 mg, 1.59 mmol) and ZSM-5 (1 g, ACSMaterial, P-38, H⁺) was heated without solvent at 100° C. for 18 hours.The reaction was cooled to room temperature and was diluted with 30 mLof TBME. The resulting suspension was filtered using a fritted Buchnerfiltering funnel. The solvent from the filtrate was evaporated in vacuo.Analysis by HPLC showed complete consumption of CBD with Δ⁸-THC as themajor product and Δ⁹-THC and cannabinol (CBN) as minor products (see,Table 2 and FIG. 5).

EXAMPLE 6: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Amberlyst-15 (500 mg). The reaction was stirred at 80° C. for2 hours. The reaction was cooled to room temperature and then filteredusing a fritted Buchner filtering funnel. The reaction solvent wasevaporated in vacuo. Analysis by HPLC showed near complete consumptionof CBD (<2% remained) with Δ⁸-THC as the major product (see, TABLE 2 andFIG. 6).

EXAMPLE 7: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added ZSM-5 (1 g, ACS Material, P-38, Na⁺). The reaction was stirredat reflux for 18 hours. The reaction was cooled to room temperature andthen filtered using a fritted Buchner filtering funnel. The reactionsolvent was evaporated in vacuo. Analysis by HPLC showed completeconsumption of CBD with Δ⁸-THC as the major product (see, TABLE 2 andFIG. 7).

EXAMPLE 8: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added ZSM-5 (1 g, ACS Material, P-38, H⁺). The reaction was stirredat reflux for 2 hours. The reaction was cooled to room temperature andthen filtered using a fritted Buchner filtering funnel. The reactionsolvent was evaporated in vacuo. Analysis by HPLC showed completeconsumption of CBD with Δ⁸-THC as the major products (see, TABLE 2 andFIG. 8).

EXAMPLE 9: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added ZSM-5 (1 g, ACS Material, P-38, H⁺). The reaction was stirredat reflux for 18 hours. The reaction was cooled to room temperature andwas filtered using a fritted Buchner filtering funnel. The reactionsolvent was evaporated in vacuo. Analysis by HPLC showed completeconsumption of CBD with Δ⁸-THC as the major product (see, TABLE 2 andFIG. 9).

EXAMPLE 10: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added Amberlyst-15 (500 mg). The reaction was stirred at roomtemperature for 2 hours. The reaction was filtered using a frittedBuchner filtering funnel, and then the reaction solvent was evaporatedin vacuo. Analysis by HPLC showed near complete consumption of CBD (<1%remained) with Δ⁸-THC as the major product and Δ⁹-THC as a minor product(see, TABLE 2 and FIG. 10).

EXAMPLE 11: To a solution of cannabidiol (500 mg, 1.59 mmol) in heptane(10 mL) was added Amberlyst-15 (50 mg). The reaction was stirred at roomtemperature for 24 hours. The reaction was filtered using a frittedBuchner filtering funnel and the reaction solvent was evaporated invacuo. Analysis by HPLC showed unreacted CBD (<12% remained) with Δ⁸-THCas the major product and Δ⁹-THC as a minor product (see, TABLE 2 andFIG. 11).

EXAMPLE 12: To a solution of CBD (500 mg, 1.59 mmol) in heptane (10 mL)was added ZSM-5 (1 g, ACS Material, P-38, H⁺). The reaction was stirredat 80° C. for 18 hours. The reaction was cooled to room temperature andthen filtered using a fritted Buchner filtering funnel. The reactionsolvent was evaporated in vacuo. Analysis by HPLC showed near completeconsumption of CBD (<2% remained) with a mixture of Δ⁸-THC Δ⁹-THC as themajor products (see, TABLE 2 and FIG. 12).

TABLE 2 HPLC results from EXAMPLES 1-12. Percentage values for CBD,Δ⁸-THC and Δ⁹-THC were determined by HPLC-DAD (215 nm). CBD Example (%)Δ⁹-THC (%) Δ⁸-THC (%) Δ⁸-THC:Δ⁹-THC 1 0.6 3.3 68.5 20.8:1.0 2 0 3.9 73.818.9:1.0 3 0.1 5.3 81.1 15.3:1.0 4 0 5.1 74.0 14.7:1.0 5 0.2 6.0 77.012.3:1.0 6 1.9 6.6 77.0 11.7:1.0 7 0 5.8 71.5 11.2:1.0 8 0.0 6.5 71.511.0:1.0 9 0 7.6 79.0 10.4:1.0 10 0.7 9.7 80.4  8.3:1.0 11 13.9 21.254.9  2.6:1.0 12 1.5 36.3 55.2  1.5:10

EXAMPLE 13: To a solution of CBD distillate (1.030 g) in heptane (20 mL)was added Al-MCM-41 (1.004 g). The reaction was stirred at 65° C. for 24hours. The supernatant was concentrated using rotary evaporator and thenfiltered. The resultant solution was evaporated to dryness usingcentrifuge evaporator. Analysis by HPLC showed near complete conversion(<1% remaining) with the major product being Δ⁸-THC (see Table 3 andFIG. 13).

TABLE 3 HPLC results from EXAMPLE 13. Percentage values for CBD, Δ⁸-THCand Δ⁹-THC were determined by HPLC-DAD (215 nm). Original distillateAl-MCM-41 at 65 C. CBD w/w % 68.35 0.24 d9-THC w/w % 2.34 2.46 d8-THCw/w % 0.04 68.71 CBN w/w % 0.38 1.04 CBDV w/w % 3.57 0 CBC w/w % 4.05 0CBL w/w % 0.52 1.17 CBT w/w % 0.52 0.82 Total cannabinoids ~78% ~75%

In the present disclosure, all terms referred to in singular form aremeant to encompass plural forms of the same. Likewise, all termsreferred to in plural form are meant to encompass singular forms of thesame. Unless defined otherwise, all technical and scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which this disclosure pertains.

As used herein, the term “about” refers to an approximately +/−10%variation from a given value. It is to be understood that such avariation is always included in any given value provided herein, whetheror not it is specifically referred to.

It should be understood that the compositions and methods are describedin terms of “comprising,” “containing,” or “including” variouscomponents or steps, the compositions and methods can also “consistessentially of” or “consist of” the various components and steps.Moreover, the indefinite articles “a” or “an,” as used in the claims,are defined herein to mean one or more than one of the element that itintroduces.

For the sake of brevity, only certain ranges are explicitly disclosedherein. However, ranges from any lower limit may be combined with anyupper limit to recite a range not explicitly recited, as well as, rangesfrom any lower limit may be combined with any other lower limit torecite a range not explicitly recited, in the same way, ranges from anyupper limit may be combined with any other upper limit to recite a rangenot explicitly recited. Additionally, whenever a numerical range with alower limit and an upper limit is disclosed, any number and any includedrange falling within the range are specifically disclosed. Inparticular, every range of values (of the form, “from about a to aboutb,” or, equivalently, “from approximately a to b,” or, equivalently,“from approximately a-b”) disclosed herein is to be understood to setforth every number and range encompassed within the broader range ofvalues even if not explicitly recited. Thus, every point or individualvalue may serve as its own lower or upper limit combined with any otherpoint or individual value or any other lower or upper limit, to recite arange not explicitly recited.

Therefore, the present disclosure is well adapted to attain the ends andadvantages mentioned as well as those that are inherent therein. Theparticular embodiments disclosed above are illustrative only, as thepresent disclosure may be modified and practiced in different butequivalent manners apparent to those skilled in the art having thebenefit of the teachings herein. Although individual embodiments aredis-cussed, the disclosure covers all combinations of all thoseembodiments. Furthermore, no limitations are intended to the details ofconstruction or design herein shown, other than as described in theclaims below. Also, the terms in the claims have their plain, ordinarymeaning unless otherwise explicitly and clearly defined by the patentee.It is therefore evident that the particular illustrative embodimentsdisclosed above may be altered or modified and all such variations areconsidered within the scope and spirit of the present disclosure. Ifthere is any conflict in the usages of a word or term in thisspecification and one or more patent(s) or other documents that may beincorporated herein by reference, the definitions that are consistentwith this specification should be adopted.

Many obvious variations of the embodiments set out herein will suggestthemselves to those skilled in the art in light of the presentdisclosure. Such obvious variations are within the full intended scopeof the appended claims.

1.-48. (canceled)
 49. A method for converting cannabidiol (CBD) intoΔ⁸-tetrahydrocannabinol (Δ⁸-THC), the method comprising contacting theCBD with a Lewis-acidic heterogeneous reagent, optionally in anaprotic-solvent system, wherein the Lewis-acidic heterogeneous reagentis an ion-exchange resin other than Amberlyst-15 or Nafion-SAC-13. 50.The method of claim 49, wherein ion-exchange resin is an Amberlystpolymeric resin which is Amberlyst-16, 31, 33, 35, 36, 39, 46, 70, CH10,CH28, CH43 or M-31, or a H⁺ or Na⁺ form thereof, or any combinationthereof.
 51. The method of claim 49, wherein the ion-exchange resin is aNafion polymeric resin which is Nafion-NR50, N115, N117, N324, N424 orN1110, or a H⁺ or Na⁺ form thereof, or any combination thereof.
 52. Themethod of claim 49, wherein the aprotic-solvent system is present. 53.The method of claim 52, wherein the aprotic-solvent system comprisesdimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, toluene,pentane, heptane, hexane, diethyl ether, tert-butyl methyl ether,tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide,N-methylpyrrolidone, anisole, butyl acetate, cumene, ethyl formate,isobutyl acetate, isopropyl acetate, methyl acetate, methylethylketone,methylisobutylketone, propyl acetate, cyclohexane, para-xylene,meta-xylene, ortho-xylene, 1,2-dichloroethane, or any combinationthereof.
 54. The method of claim 52, wherein the aprotic-solvent systemis heptane.
 55. The method of claim 49, wherein the Δ⁸-THC is acomponent of a composition that further comprisesΔ⁹-tetrahydrocannabinol (Δ⁹-THC), and wherein the composition has aΔ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.
 56. A method forconverting cannabidiol (CBD) into Δ⁸-tetrahydrocannabinol (Δ⁸-THC), themethod comprising contacting the CBD with a Lewis-acidic heterogeneousreagent, optionally in an aprotic-solvent system, wherein theLewis-acidic heterogeneous reagent is a microporous silicate, andwherein the Δ⁸-THC is a component of a composition that furthercomprises Δ⁹-tetrahydrocannabinol (Δ⁹-THC), and wherein the compositionhas a Δ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.
 57. The methodof claim 56, wherein the microporous silicate other than Zeolite Y,Zeolite Beta, SAPO-11 or SAPO-11.
 58. The method of claim 56, whereinthe microporous silicate is a zeolite which is ZSM-5, ZSM-11, ZSM-22,ZSM-23, ZSM-35, SAPO-34, SSZ-13, TS-1, X-type, Linde type A, Linde typeL, Linde type X, or Linde type Y, or a H+ or Na+ form thereof, or anycombination thereof.
 59. The method of claim 56, wherein theaprotic-solvent system is present.
 60. The method of claim 59, whereinthe aprotic-solvent system comprises dimethyl sulfoxide, ethyl acetate,dichloromethane, chloroform, toluene, pentane, heptane, hexane, diethylether, tert-butyl methyl ether, tetrahydrofuran, dioxane,dimethylformamide, dimethylacetamide, N-methylpyrrolidone, anisole,butyl acetate, cumene, ethyl formate, isobutyl acetate, isopropylacetate, methyl acetate, methylethylketone, methylisobutylketone, propylacetate, cyclohexane, para-xylene, meta-xylene, ortho-xylene,1,2-dichloroethane, or any combination thereof.
 61. The method of claim59, wherein the aprotic-solvent system is heptane.
 62. A method forconverting cannabidiol (CBD) into Δ⁸-tetrahydrocannabinol (Δ⁸-THC), themethod comprising contacting the CBD with a Lewis-acidic heterogeneousreagent, optionally in an aprotic-solvent system, wherein theLewis-acidic heterogeneous reagent is a mesoporous silicate or aphyllosilicate.
 63. The method of claim 62, wherein the Lewis-acidicheterogeneous reagent is the mesoporous silicate, and the mesoporoussilicate is Al-MCM-41, MCM-41, MCM-48, SBA-15, SBA-16, KIT-5, KIT-6,FDU-12, or any combination thereof.
 64. The method of claim 62, whereinthe Lewis-acidic heterogeneous reagent is the phyllosilicate, and thephyllosilicate is Faujasite, Mordenite, Ferrierite, Montmorillonite K10,Montmorillonite K20, Montmorillonite K30, Montmorillonite KSF, Clayzic,or bentonite, or any combination thereof.
 65. The method of claim 64,wherein the phyllosilicate is Montmorillonite K10, Montmorillonite K20,Montmorillonite K30 or Montmorillonite KSF.
 66. The method of claim 62,wherein the aprotic-solvent system is present.
 67. The method of claim66, wherein the aprotic-solvent system comprises dimethyl sulfoxide,ethyl acetate, dichloromethane, chloroform, toluene, pentane, heptane,hexane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran,dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidone,anisole, butyl acetate, cumene, ethyl formate, isobutyl acetate,isopropyl acetate, methyl acetate, methylethylketone,methylisobutylketone, propyl acetate, cyclohexane, para-xylene,meta-xylene, ortho-xylene, 1,2-dichloroethane, or any combinationthereof.
 68. The method of claim 66, wherein the aprotic-solvent systemis heptane.
 69. The method of claim 62, wherein the Δ⁸-THC is acomponent of a composition that further comprisesΔ⁹-tetrahydrocannabinol (Δ⁹-THC), and wherein the composition has aΔ⁸-THC:Δ⁹-THC ratio that is greater than 1.0:1.0.